Preparation of smectic itraconazole nanoparticles with tunable periodic order using microfluidics-based anti-solvent precipitation

Abstract

Nanoparticles with liquid crystalline structure have the combinational advantages of large surface area and compromised molecular order, leading to enhanced solubility and dissolution rate compared to their crystalline counterparts, as well as improved stability in contrast to their amorphous forms. Microfluidics-based anti-solvent precipitation emerges as a promising approach for the continuous and scalable production of liquid crystalline nanoparticles of the desired size and structure. This study outlines a microfluidics-based anti-solvent precipitation approach, capable of generating monodisperse liquid crystalline nanoparticles in a controllable manner, using itraconazole (ITZ) as a model drug. Moreover, the mixing performance in the microfluidic device under different temperatures and solvent/antisolvent (S/AS) ratios was demonstrated to be readily visualized by a laser-induced fluorescence (LIF) system, which reinforces proper control over the precipitation process in the micro-channels. The size, morphology and the structure of the liquid crystalline nanoparticles prepared at different temperatures were investigated. We demonstrated that the periodic order of liquid crystalline ITZ was precipitation temperature-dependent, and therefore, could be fine-tuned by temperature control.